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Background: Medicines complement healthy lifestyles in cardiovascular disease (CVD) prevention, but knowledge is lacking on how behaviours in these domains are related. This study aimed at investigating associations between physical activity and diet, and time to initiation of preventive medicines.

Method: A cohort study based on the "Visualization of Asymptomatic Atherosclerotic Disease for Optimal Cardiovascular Prevention" (VIPVIZA)-trial, including 60-year-olds of low/moderate CVD-risk who were treatment-naive to antihypertensives or lipid-lowering medicines six months prior trial-inclusion. Sex-specific Cox proportional hazards models were used to analyse impacts of diet and physical activity, each categorized in three levels (least healthy – moderately healthy – healthiest), on initiation of antihypertensives and lipid-lowering medicines.

Results: Of 1891 individuals in the cohort, 1340 (58% women) were antihypertensive-naive and 1783 (57% women) were lipid-lowering naive. Significantly faster initiation of antihypertensives was seen in women with the healthiest diet (HR [95%CI] 2.46 [1.18–5.14], ref. least healthy) whereas higher levels of physical activity were significantly associated with slower initiation of antihypertensives in women (HR [95%CI], moderate; 0.51 [0.30–0.88]), high; 0.48 [0.30–0.77], ref. low). Neither diet nor physical activity levels affected initiation of lipid-lowering medicines in women, and lifestyle factors were not associated with initiation of antihypertensives or lipid-lowering medicines in men.

Conclusions: Relationships between lifestyle and medicine initiation varies with health behavior, drug-class, and sex. Regarding diet, initiation of antihypertensives in women may agree with a healthy adherer effect, whereas for physical activity, the association appear inverse. Diet and physical activity levels are less influential for initiation in men, and for lipid-lowering medicines. As findings are uncertain, further studies are needed to clarify relationships between these factors.

Trial registration: VIPVIZA-trial registration number: NCT01849575, registration date: 2013-05-08.

Aims: The Västerbotten Intervention Programme VIsualiZation of subclinical Atherosclerosis (VIPVIZA) pragmatic randomized controlled trial (RCT) previously reported reduced cardiovascular disease (CVD) risk 3 years after colour-coded information about subclinical atherosclerosis based on carotid ultrasonography and facilitated by nurse-led motivational dialogue. This report evaluated the development of CVD risk and clinical risk factors following the 3-year follow-up, at which point the control group received their first delayed intervention and the intervention group received a repeated VIPVIZA intervention.

Methods and results: Participants (n = 3532) were recruited during 2013–2016 and randomized into two groups. Routine primary care managed preventive treatments. At the 6-year follow-up, group differences in CVD risk factors, the European Systematic Coronary Risk Evaluation 2 (SCORE2), and Framingham Risk Score (FRS) were statistically tested. Trajectories of the outcomes in both groups were graphically assessed. The participation rate after 6 years was 75.4%. No significant differences were found between groups in levels of SCORE2, FRS, clinical risk factors, anthropometrics, smoking, or diabetes—except for systolic blood pressure, which was lower in the original intervention group. Risk scores and systolic blood pressure increased in both groups in parallel, while LDL levels decreased and converged. The higher the baseline risk was, the stronger the decrease of LDL cholesterol.

Conclusion: When the delayed VIPVIZA intervention was provided to the control group after 3 years, the beneficial effect appeared similar as previously reported for the intervention group. After 6 years, any differences between groups in CVD risk were no longer seen. Cholesterol levels were greatly reduced in both groups.

Registration: The VIPVIZA trial is registered with www.clinicaltrials.gov (NCT01849575).

Background: Alcohol consumption at low to moderate levels has long been debated in relation to cardiovascular risk, with inconsistent findings. Multi-decade cohort data with repeated exposure assessments are rare, especially in a northern Scandinavian population. This study aims to investigate associations between alcohol consumption at age 40, 50, and 60 and markers of subclinical atherosclerosis [carotid plaque and intima-media thickness (IMT)] at age 60 in a healthy below-risk-threshold alcohol-consuming cohort in Northern Sweden.

Methods: Participants in the Visualisation of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention (VIPVIZA) trial, aged 60 and with alcohol data from the Västerbotten Intervention Programme (VIP) at 40, 50, and 60, with below-risk-threshold alcohol consumption (>0 to ≤100 g/week) (n = 1,014) were included. Alcohol intake data were collected via a food frequency questionnaire in VIP. Carotid plaque and IMT were assessed at age 60 at VIPVIZA baseline.

Results: Mean weekly alcohol consumption for the study period was 26 g (±21.4 g), higher in men (37.5 ± 23.8 g) than in women (19.2 ± 16.3 g) and increasing over time in both sexes. At age 60, 49.6% had carotid plaque, and mean IMT was 0.77 mm (±0.15). No indication of associations was found between midlife alcohol consumption and carotid plaque in the total cohort [odds ratio (OR): 1.00, 95% confidence interval (CI): 0.99–1.01], men (OR: 1.00, 95% CI: 0.99–1.01), or women (OR: 0.99, 95% CI: 0.99–1.00) per gram increase of weekly alcohol intake. No associations were observed across consumption groups (>25 to ≤50, >50 to ≤75, >75 to ≤100 vs. >0 to ≤25 g/week).

Conclusion: No association was found between self-reported midlife alcohol consumption and subclinical atherosclerosis at age 60 in the VIPVIZA baseline cohort. Results were consistent across sexes and intake levels, contributing to the evidence base used to guide primary prevention and public health recommendations.

Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with a well-recognized increased risk of thrombotic events, bleeding, and all-cause mortality, but the frequency of these outcomes during treatment has rarely been assessed in large cohorts.

Methods: In this nationwide, population-based study, we analyzed 2604 PV and 3141 ET patients using multiple Swedish health care registers, covering 43 612 patient-years. Rates of arterial and venous events, major bleeding, and all-cause mortality (ACM) were evaluated across therapies.

Results: Unexpectedly, 42.3% of low-risk PV patients and 29.7% of very low/low-risk ET patients received hydroxyurea (HU) during follow-up. High-risk PV patients treated with interferon (IFN) exhibited the lowest arterial event rate (2.21 per 100 patient-years). In high-risk ET, patients with IFN therapy experienced the lowest arterial and venous event rates (1.55 and 0.44 per 100 patient-years). Advanced age and leukocytosis at diagnosis independently predicted thrombosis, bleeding, and ACM in both PV and ET. Multivariable analysis showed that HU and IFN were associated with reduced ACM risk; HU also conferred protection against thromboembolism and major bleeding.

Conclusion: This study highlights risk factors associated with complications during treatment in a real-world context and reinforces the role of HU and IFN as first-line therapies in PV and ET.

Purpose. To quantify the risk of clinically overt venous thromboembolism (VTE) and major bleeding (MB) during the first year following surgery for lumbar spinal stenosis (LSS) relative to a matched population cohort.

Methods: This nationwide, retrospective cohort study utilized data from the Swedish National Spine Register (Swespine), including 77,145 patients who underwent surgical treatment for LSS between 2003 and 2023. These patients were matched 1:5 to 385,388 referents from the general population. Outcomes (VTE and MB) were identified through cross-linkage with the National Patient Register (NPR) and the Swedish Stroke Register (Riksstroke). Adjusted Cox piecewise regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE and MB across prespecified postoperative intervals.

Results: Within the first 30 days after inclusion, patients exhibited substantially higher incidence rates of venous thromboembolism (VTE) and major bleeding (MB) compared with referents. The incidence rate of VTE was 30.39 per 1,000 person-years among patients versus 8.14 among referents, while the corresponding rates for MB were 88.78 and 31.87 per 1,000 person-years, respectively. Compared with referents, patients had a HR of 3.68 (95% CI, 3.05-4.44) for VTE and a HR of 2.52 (95% CI 2.27-2.80) for MB within the first 30 days after inclusion. The risk for VTE remained elevated through the 31–60-day interval (HR 2.09; 95% CI, 1.63-2.69), whereas the risk for MB declined sharply after the first month (HR 1.02; 95% CI 0.87-1.21).

Conclusion: Patients undergoing surgery for LSS face a significantly higher risk for VTE and MB compared to a matched population. This hazard was most acute during the first 30 postoperative days. While these risks decline sharply thereafter, the risk of VTE remains significantly elevated during the first 2 months following LSS surgery.

Background: High alcohol intake has many negative health effects, but its association with venous thromboembolism (VTE) is based on self-reported consumption and is unclear. This study aimed to investigate the association between alcohol consumption measured by the biomarker phosphatidylethanol (PEth) and risk of first-ever VTE.

Methods: We conducted a population-based nested case-referent study in northern Sweden. The study is based on the Västerbotten Intervention Programme VIP which includes health examinations and prospective blood sampling. Cases of objectively verified first-ever VTE between 1985 and 2014 were registered. Referents were matched for age, sex, health examination date, geographical area, and sample freeze-thaw cycles. In 2024, PEth concentrations were measured using a liquid chromatography tandem-mass spectrometry method with a limit of quantification of 0.01 μmol/L.

Results: The study included 1410 cases with objectively verified VTE and 1410 matched referents. The median age of cases at the health examination was 50.2 years, and 55.2 % of cases were men. We found an association between the highest PEth concentration category (>0.30 μmol/L) and risk of VTE (odds ratio 1.44 [95 % confidence interval 1.05–1.98]) compared to the lowest concentration category (PEth <0.01 μmol/L) in a model adjusted for education level, body mass index, smoking, hypertension, and cancer at inclusion.

Conclusions: A high PEth concentration was independently associated with an increased risk of first-ever VTE. Furthermore, the study highlights the benefits of PEth as a biomarker to identify individuals with high alcohol consumption that are at an increased risk of adverse medical outcomes.

Background: The ABO blood group system has shown an association with cardiovascular disease. The susceptibility to CVD is proposed to be partly mediated by dyslipidaemia in non-O individuals. Previous studies are scarce for the RhD blood group, but we recently showed that RhD − young individuals are associated with subclinical atherosclerosis. Hence, we sought to examine whether the ABO blood groups and RhD factor are associated with dyslipidaemia.

Methods: All participants were part of the VIPVIZA study, including 3532 individuals with available plasma lipid levels. Lipids were assessed as total, LDL, HDL, remnant, non-HDL cholesterol and triglycerides. Information about ABO and RhD was retrieved by linking VIPVIZA with the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.

Results: For the ABO blood groups, no significant differences in lipid levels between non-O and O individuals were seen. In 40-year-old males, RhD − individuals compared to RhD + had higher levels of non-HDL cholesterol, LDL cholesterol, and remnant cholesterol, with ratios of geometric means of 1.21 (CI95% 1.03; 1.43), 1.20 (1.02; 1.41) and 1.38 (1.00; 1.92), respectively. No differences in lipid levels depending on the RhD blood group were seen in women or the older age groups.

Conclusion: Our study indicates that younger RhD − men have increased non-HDL, LDL, and remnant cholesterol levels. Thus, the RhD blood group, but not ABO, seems to be associated with dyslipidaemia and may act as a future possible risk marker of cardiovascular disease.

OBJECTIVES: To investigate if beliefs about medicines affect the time to the initiation of cardiovascular preventive medications during a 3 year follow-up period.

DESIGN: A questionnaire and register-based cohort study.

SETTING: Primary care in Sweden, in which people 40, 50 and 60 years old underwent risk factor screening and individual health promotion within the Västerbotten intervention programme (VIP).

PARTICIPANTS: People at low/medium risk of cardiovascular disease (CVD) according to the risk factor screening were included in the VIsualiZation of asymptomatic Atherosclerotic disease for optimum cardiovascular prevention-a population-based Pragmatic Randomised Open Blinded End-point trial (PROBE) nested in the Västerbotten Intervention Programme (VIPVIZA), aiming at improved primary prevention of CVD. People participating in the VIPVIZA 3 year follow-up (n=3167 (89.7%)), receiving the Beliefs about medicines questionnaire (BMQ) (n=2314 (73.1%)) and with complete answers to at least one subscale in the BMQ general (n=2258 (97.6%)) were included. Moreover, only those 60 years old at baseline (n=2073 (58.7%)) and without antihypertensive and/or lipid-lowering drugs (n=1769 (50.1%)) 6 months prior to inclusion in the VIPVIZA trial were included. Accordingly, the final study population comprised 888 people without antihypertensive medicines and 1185 without lipid-lowering drugs, respectively.

MEASURES: The primary outcome was time to the binary event of initiating antihypertensives or lipid-lowering agents, identified within the time frame from inclusion in the VIPVIZA study until the study participants' 3 year follow-up visit. General beliefs about medicines were assessed according to the BMQ. Cox proportional hazards models, adjusted for sex, were conducted to investigate primary outcome. RESULTS: Participants with stronger general beliefs about medicines being overused had significantly longer time to initiation of antihypertensive drugs in the control group (HR 0.91; 95% CI 0.84 to 0.996) but not in the intervention group (HR 1.05; 95% CI 0.95 to 1.16). No significant associations were found between beliefs about medicines and initiation of lipid-lowering treatment.

CONCLUSIONS: A more negative perception of drugs being overused was significantly associated with delayed initiation of antihypertensive drug treatment. Our results suggest that the VIPVIZA intervention may overbridge negative perceptions and affect the initiation of antihypertensive medications in a positive manner.

TRIAL REGISTRATION NUMBER: NCT01849575 (date of registration: 8 May 2013).

BACKGROUND: – The clinical use of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score–guided multidimensional treatment strategy improves long-term outcomes in patients with AF.

METHODS: – The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the ABC-AF strategy arm, the investigator was informed of each individual’s ABC-AF score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct oral anticoagulant treatment. In the standard of care arm, patient management was at the discretion of the investigator. Primary outcome was a composite of stroke or death. Secondary outcomes included stroke, death, major bleeding events, and their composite outcome.

RESULTS: – The intention-to-treat population comprised 3933 patients with a median age of 73.7 years; 33.6% were women, 51.3% had paroxysmal AF, 11.2% had a previous stroke or transient ischemic attack, and 85.7% had oral anticoagulant treatment. After randomization, 97.8% in the ABC-AF strategy arm and 92.6% in the standard of care arm received OACs (P<0.0001). Enrollment was prematurely terminated owing to safety concerns with a trend toward higher mortality in patients with CHA2DS2-VASc scores of ≥3, and the study was therefore underpowered for its primary objective. Over a median follow-up of 2.6 years, 175 primary events (3.18/100 patient-years [100PY]) occurred in the ABC-AF strategy and 148 (2.67/100PY) in the standard of care arm (hazard ratio [HR], 1.19 [95% CI, 0.96–1.48]; P=0.12). Major bleeding events were 152 (2.82/100PY) versus 141 (2.61/100PY; HR, 1.08 [95% CI, 0.86–1.36]; P=0.50), stroke 48 (0.87/100PY) versus 41 (0.74/100PY; HR, 1.18 [95% CI, 0.78–1.79]; P=0.44), death 136 (2.44/100PY) versus 113 (2.02/100PY; HR, 1.21 [95% CI, 0.94–1.55]; P=0.13), and rates of composite stroke, death, or major bleeding 277 (5.21/100PY) versus 244 (4.55/100PY; HR, 1.14 [95% CI, 0.96–1.36]; P=0.13). Primary outcome results were similar across ABC-AF score subgroups (interaction P=0.98).

CONCLUSIONS: – The individually tailored multidimensional treatment strategy, based on ABC-AF risk scores, did not improve clinical outcomes compared with usual guideline-based care in patients with AF. The results emphasize the need for prospective testing of the use of risk stratification and precision medicine tools in different clinical settings before implementation in routine care. REGISTRATION: – URL: https://www.clinicaltrials.gov; Unique identifier: NCT03753490.

Introduction: Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are superior or non-inferior to warfarin in reducing the risk of stroke while at the same time having a similar or lower risk of bleeding. However, reduced doses are prescribed more often than expected from clinical practice and off-label underdosing is a frequent issue. The objective of this study was to compare effectiveness and safety between guideline and off-label dosing of DOACs.

Materials and methods: Auricula, a Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 47,355 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) after exclusion of 92,316 patients due to concomitant venous thromboembolism, previous mechanical heart valve (MHV) or previous data entry in Auricula. The median durations of follow up were 403, 419, 373 and 209 days in the on-label standard dose cohort, off-label reduced dose cohort, on-label reduced dose cohort and the off-label standard dose cohort respectively. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes or the Swedish Stroke register. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores.

Results: Off-label underdosing of DOACs (n = 6,187, 9.7 %) was associated with higher risk of major bleeding HR 1.16 (95 % CI 1.05–1.27), other bleeding HR 1.16 (1.04–1.30), myocardial infarction HR 1.47 (1.20–1.80), ischemic stroke HR 1.25 (1.04–1.50) and all-cause mortality HR 1.52 (1.37–1.69) compared to on-label standard dosing (n = 35,065, 55.2 %). Among off-label underdosed DOACs, dabigatran was associated with higher risk of all-cause stroke 1.86 (1.07–3.23), ischemic stroke HR 1.97 (1.10–3.52) and all-cause stroke and systemic embolism HR 1.92 (1.11–3.32) compared to apixaban. Rivaroxaban was associated with major bleeding HR 1.70 (1.41–2.03), gastrointestinal bleeding HR 1.92 (1.33–2.77), and other bleeding HR 1.97 (1.57–2.47) compared to apixaban. The study could not show any differences comparing off-label overdosing of DOACs and on-label reduced dosing, besides lower risk of all-cause mortality HR 0.69 (0.52–0.93) in the overdosed patients.

Conclusions: In this large observational registry-based NVAF cohort, underdosing of DOACs is associated with higher risk of ischemic and all-cause stroke but also major bleeding when compared to on-label dosing. Underlying DOAC therapy may need to be tailored to the specific patient when choosing off-label reduced dosing since underdosed rivaroxaban is associated with higher risk of bleeding complications, and underdosed dabigatran is associated with higher risk of stroke complications, when comparing both with apixaban.